US2009048301A1PendingUtilityA1
Heterocyclic compounds and their use as anticancer agents
Est. expiryJul 9, 2023(expired)· nominal 20-yr term from priority
Inventors:Xiaoling ChenHai-Ying HeJoel KawakamiAlexander KiselyovXiaohu OuyangVatee PattaropongEvgueni Lvovich PiatnitskiMaria Carolina TumaJohn Kincaid
C07D 413/04C07D 413/14C07D 401/14C07D 413/12C07D 401/04C07D 405/14A61P 35/00C07D 401/12C07D 263/48C07D 405/12C07D 249/14
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Claims
Abstract
The present invention relates to heterocyclic compounds that have anticancer activity, and pharmaceutical compositions that contain such compounds, methods of treating diseases and conditions in mammals using such compounds and composition and methods for their manufacture.
Claims
exact text as granted — not AI-modified1 . A compound having Formula II:
or pharmaceutically acceptable salts, stereoisomers, hydrates or pro-drugs thereof, wherein,
the ring formed by T, U, V is
Z is O, S, nitro, or NR 4 ;
R 1 , R 2 , or R 5 each independently is:
1) hydrogen, hydroxyl, halo, nitro, or cyano;
2) C 1 -C 8 alkyl;
3) C 2 -C 8 alkenyl;
4) C 2 -C 8 alkynyl;
5) C 1 -C 8 alkoxy;
6) C 3 -C 8 cycloalkyl or heterocyclyl;
7) C 4 -C 8 cycloalkylalkyl or heterocyclylalkyl;
8) C 3 -C 10 aryl;
9) C 5 -C 10 aralkyl;
10) C 6 -C 10 aryloxy;
11) NH 2 , NHR 7 , or NR 7 R 7 ; or
12) —SO 2 R 7 ,
wherein R 7 is independently H, hydroxyl, halo, C 1 -C 6 alkyl optionally substituted with at least one R 10 , C 1 -C 6 alkoxy optionally substituted with at least one R 10 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 10 , C 4 -C 8 heterocycloalkyl optionally substituted with at least one R 10 , C 3 -C 10 aryl optionally substituted with at least one R 10 , NH 2 , NHR 10 , NR 10 R 10 , or SO 2 R 10 , wherein R 10 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or NH 2 ; optionally, R 1 and R 2 taken together form a ring structure including cycloalkyl, heterocyclyl, or aryl ring;
R 3 is:
1) hydrogen;
2) C 1 -C 8 alkyl;
3) C 2 -C 8 alkenyl;
4) C 2 -C 8 alkynyl;
5) C 1 -C 8 alkoxy;
6) C 3 -C 10 cycloalkyl or heterocyclyl;
7) C 4 -C 10 cycloalkylalkyl or heterocyclylalkyl;
8) C 3 -C 10 aryl;
9) C 4 -C 10 aralkyl;
10) carbonyl; or
11) —SO 2 R 8 , —CO 2 R 8 , —SR 8 , or —SOR 8 ;
wherein R 8 is independently H, halo, cyano, nitro, C 1 -C 4 alkyl optionally substituted with at least one R 11 , C 1 -C 4 alkoxy optionally substituted with at least one R 11 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 11 , C 3 -C 8 heterocyclyl optionally substituted with at least one R 11 , C 6 -C 10 aryl optionally substituted with at least one R 11 , C 6 -C 10 aralkyl optionally substituted with at least one R 11 , NH 2 , NHR 11 , NR 11 R 11 , or SO 2 R 11 , wherein R 11 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 6 -C 10 aryl, C 3 -C 8 aralkyl, C 3 -C 8 heterocyclyl, or NH 2 ,
R 4 is:
1) hydrogen;
2) C 1 -C 8 alkyl;
3) C 2 -C 8 alkenyl;
4) C 2 -C 8 alkynyl;
5) C 3 -C 8 cycloalkyl or heterocyclyl;
6) C 4 -C 8 cycloalkylalkyl or heterocyclylalkyl;
7) C 3 -C 10 aryl;
8) C 5 -C 10 aralkyl;
9) carbonyl; or
10) —SO 2 R 12 , or —SOR 12 ;
wherein R 12 is independently H, halo, cyano, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 13 , C 1 -C 4 alkoxy optionally substituted with at least one R 13 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 13 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 13 , C 3 -C 10 aryl optionally substituted with at least one R 13 , NH 2 , NHR 13 , NR 13 R 13 , or SO 2 R 13 , wherein R 13 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 8 aryl, C 3 -C 8 heterocyclylalkyl, or NH 2 ; optionally, R 3 and R 4 are taken together to form a C 4 -C 6 heterocyclyl optionally substituted with R 13 , or aryl; and
R 6 is:
1) C 1 -C 8 alkyl;
2) C 2 -C 8 alkenyl;
3) C 2 -C 8 alkynyl;
4) C 1 -C 8 alkoxy;
5) C 3 -C 10 cycloalkyl or heterocyclyl;
6) C 4 -C 10 cycloalkylalkyl or heterocyclylalkyl;
7) C 4 -C 10 aryl;
8) C 5 -C 10 aralkyl; or
9) NH 2 , NHR 9 or NR 9 R 9 ,
wherein R 9 is independently hydroxyl, halo, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 14 , C 2 -C 6 alkynyl optionally substituted with at least one R 14 , C 1 -C 6 alkoxy optionally substituted with at least one R 14 , C 3 -C 10 cycloalkyl optionally substituted with at least one R 14 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 14 , C 4 -C 8 cycloalkylalkyl optionally substituted with R 14 , heterocyclylalkyl optionally substituted with R 14 , C 4 -C 10 aryl optionally substituted with at least one R 14 , C 5 -C 10 aralkyl optionally substituted with at least one R 14 , —NH 2 , —NHR 14 , —NR 14 R 14 , or —SO 2 —R 14 , wherein R 14 is independently halo, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 4 -C 9 cycloalkyl, C 4 -C 9 heterocycloalkyl, C 4 -C 10 aryl, —SO 2 (C 6 -C 10 aryl), —NH 2 , —NH[(C 1 -C 4 ) alkyl], —N[(C 1 -C 4 ) alkyl] 2 , —NH(C 5 -C 8 heterocyclylalkyl), —NH(C 6 -C 8 aryl), or —NH(C 6 -C 8 heterocyclyl).
2 . The compounds according to claim 1 , wherein Z is O or NH.
3 . The compounds according to claim 1 , wherein R 1 , R 2 , or R 5 is substituted with R 7 , wherein R 7 is independently hydroxyl, halo, C 1 -C 6 alkyl optionally substituted with at least one R 10 , C 1 -C 6 alkoxy optionally substituted with at least one R 10 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 10 , C 4 -C 8 heterocycloalkyl optionally substituted with at least one R 10 , C 3 -C 10 aryl optionally substituted with at least one R 10 , NH 2 , NHR 10 , NR 10 R 10 , or SO 2 R 10 , wherein R 10 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or NH 2 .
4 . The compounds according to claim 1 , wherein R 1 and R 2 taken together form a ring structure including cycloalkyl, heterocyclyl or aryl rings.
5 . The compound according to claim 1 , wherein R 3 is substituted with R 8 wherein R 8 is independently halo, cyano, nitro, C 1 -C 4 alkyl optionally substituted with at least one R 11 , C 1 -C 4 alkoxy optionally substituted with at least one R 11 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 11 , C 3 -C 8 heterocyclyl optionally substituted with at least one R 11 , C 6 -C 10 aryl optionally substituted with at least one R 11 , C 6 -C 10 aralkyl optionally substituted with at least one R 11 , NH 2 , NHR 11 , NR 11 R 11 , or SO 2 R 11 , wherein R 11 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 6 -C 10 aryl, C 3 -C 8 aralkyl, C 3 -C 8 heterocyclyl, or NH 2 .
6 . The compound according to claim 1 , wherein R 4 is substituted with R 12 wherein R 12 is independently halo, cyano, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 13 , C 1 -C 4 alkoxy optionally substituted with at least one R 13 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 13 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 13 , C 3 -C 10 aryl optionally substituted with at least one R 13 , NH 2 , NHR 13 , NR 13 R 13 , or SO 2 R 13 , wherein R 13 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 8 aryl, C 3 -C 8 heterocyclylalkyl, or NH 2 .
7 . The compound according to claim 1 , wherein R 6 is substituted with R 9 wherein R 9 is independently hydroxyl, halo, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 14 , C 2 -C 6 alkynyl optionally substituted with at least one R 14 , C 1 -C 6 alkoxy optionally substituted with at least one R 14 , C 3 -C 10 cycloalkyl optionally substituted with at least one R 14 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 14 , C 4 -C 8 cycloalkylalkyl optionally substituted with R 14 , heterocyclylalkyl optionally substituted with R 14 , C 4 -C 10 aryl optionally substituted with at least one R 14 , C 5 -C 10 aralkyl optionally substituted with at least one R 14 , —NH 2 , —N 14 , —NR 14 R 14 , or —SO 2 —R 14 , wherein R 14 is independently halo, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 4 -C 9 cycloalkyl, C 4 -C 9 heterocycloalkyl, C 4 -C 10 aryl, —SO 2 (C 6 -C 10 aryl), —NH 2 , —NH[(C 1 -C 4 ) alkyl], —N[(C 1 -C 4 ) alkyl] 2 , —NH(C 5 -C 8 heterocyclylalkyl), —NH(C 6 -C 8 aryl), or —NH(C 6 -C 8 heterocyclyl).
8 . A compound of Formula III:
wherein,
the ring formed by T, U, V is
Z is O, S, nitro, or NR 4 ;
R 1 , R 2 , or R 5 each independently is:
1) hydrogen, hydroxyl, halo, nitro, or cyano;
2) C 1 -C 8 alkyl;
3) C 2 -C 8 alkenyl;
4) C 2 -C 8 alkynyl;
5) C 1 -C 8 alkoxy;
6) C 3 -C 8 cycloalkyl or heterocyclyl;
7) C 4 -C 8 cycloalkylalkyl or heterocyclylalkyl;
8) C 3 -C 10 aryl;
9) C 5 -C 10 aralkyl;
10) C 6 -C 10 aryloxy;
11) NH 2 , NHR 7 , or NR 7 R 7 ; or
12) —SO 2 R 7 ,
wherein R 7 is independently H, hydroxyl, halo, C 1 -C 6 alkyl optionally substituted with at least one R 10 , C 1 -C 6 alkoxy optionally substituted with at least one R 10 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 10 , C 4 -C 8 heterocycloalkyl optionally substituted with at least one R 10 , C 3 -C 10 aryl optionally substituted with at least one R 10 , NH 2 , NHR 10 , NR 10 R 10 , or SO 2 R 10 , wherein R 10 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or NH 2 ; optionally, R 1 and R 2 taken together form a ring structure including cycloalkyl, heterocyclyl, or aryl ring;
R 3 is:
1) hydrogen;
2) C 1 -C 8 alkyl;
3) C 2 -C 8 alkenyl;
4) C 2 -C 8 alkynyl;
5) C 1 -C 8 alkoxy;
6) C 3 -C 10 cycloalkyl or heterocyclyl;
7) C 4 -C 10 cycloalkylalkyl or heterocyclylalkyl;
8) C 3 -C 10 aryl;
9) C 4 -C 10 aralkyl;
10) carbonyl; or
11) —SO 2 R 8 , —CO 2 R 8 , —SR 8 , or —SOR 8 ;
wherein R 8 is independently H, halo, cyano, nitro, C 1 -C 4 alkyl optionally substituted with at least one R 11 , C 1 -C 4 alkoxy optionally substituted with at least one R 11 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 11 , C 3 -C 8 heterocyclyl optionally substituted with at least one R 11 , C 6 -C 10 aryl optionally substituted with at least one R 11 , C 6 -C 10 aralkyl optionally substituted with at least one R 11 , NH 2 , NHR 11 , NR 11 R 11 , or SO 2 R 11 , wherein R 11 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 6 -C 10 aryl, C 3 -C 8 aralkyl, C 3 -C 8 heterocyclyl, or NH 2 ,
R 4 is:
1) hydrogen;
2) C 1 -C 8 alkyl;
3) C 2 -C 8 alkenyl;
4) C 2 -C 8 alkynyl;
5) C 3 -C 8 cycloalkyl or heterocyclyl;
6) C 4 -C 8 cycloalkylalkyl or heterocyclylalkyl;
7) C 3 -C 10 aryl;
8) C 5 -C 10 aralkyl;
9) carbonyl; or
10) —SO 2 R 12 , or —SOR 12 ;
wherein R 12 is independently H, halo, cyano, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 13 , C 1- C 4 alkoxy optionally substituted with at least one R 13 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 13 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 13 , C 3 -C 10 aryl optionally substituted with at least one R 13 , NH 2 , NHR 13 , NR 13 R 13 , or SO 2 R 13 , wherein R 13 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 8 aryl, C 3 -C 8 heterocyclylalkyl, or NH 2 ; optionally, R 3 and R 4 are taken together to form a C 4 -C 6 heterocyclyl optionally substituted with R 13 , or aryl; and
R 6 is:
1) C 1 -C 8 alkyl;
2) C 2 -C 8 alkenyl;
3) C 2 -C 8 alkynyl;
4) C 1 -C 8 alkoxy;
5) C 3 -C 10 cycloalkyl or heterocyclyl;
6) C 4 -C 10 cycloalkylalkyl or heterocyclylalkyl;
7) C 4 -C 10 aryl;
8) C 5 -C 10 aralkyl; or
9) NH 2 , NHR 9 or NR 9 R 9 ,
wherein R 9 is independently hydroxyl, halo, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 14 , C 2 -C 6 alkynyl optionally substituted with at least one R 14 , C 1 -C 6 alkoxy optionally substituted with at least one R 14 , C 3 -C 10 cycloalkyl optionally substituted with at least one R 14 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 14 , C 4 -C 8 cycloalkylalkyl optionally substituted with R 14 , heterocyclylalkyl optionally substituted with R 14 , C 4 -C 10 aryl optionally substituted with at least one R 14 , C 5 -C 10 aralkyl optionally substituted with at least one R 14 , —NH 2 , —NHR 14 , —NR 14 R 14 , or —SO 2 —R 14 , wherein R 14 is independently halo, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 4 -C 9 cycloalkyl, C 4 -C 9 heterocycloalkyl, C 4 -C 10 aryl, —SO 2 (C 6 -C 10 aryl), —NH 2 , —NH[(C 1 -C 4 ) alkyl], —N[(C 1 -C 4 ) alkyl] 2 , —NH(C 5 -C 8 heterocyclylalkyl), —NH(C 6 -C 8 aryl), or —NH(C 6 -C 8 heterocyclyl).
9 . The compound according to claim 8 , wherein Z is O or NR 4 .
10 . The compound according to claim 8 , wherein R 1 , R 2 , or R 5 is substituted with R 7 wherein R 7 is independently hydroxyl, halo, C 1 -C 6 alkyl optionally substituted with at least one R 10 , C 1 -C 6 alkoxy optionally substituted with at least one R 10 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 10 , C 4 -C 8 heterocycloalkyl optionally substituted with at least one R 10 , C 3 -C 10 aryl optionally substituted with at least one R 10 , NH 2 , NHR 10 , NR 10 R 10 , or SO 2 R 10 , wherein R 10 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or NH 2 .
11 . The compound according to claim 8 , wherein when taken together R 1 and R 2 form a ring structure including cycloalkyl, heterocyclyl, or aryl.
12 . The compound according to claim 8 , wherein R 3 is substituted with R 8 wherein R 8 is independently halo, cyano, nitro, C 1 -C 4 alkyl optionally substituted with at least one R 11 , C 1 -C 4 alkoxy optionally substituted with at least one R 11 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 11 , C 3 -C 8 heterocyclyl optionally substituted with at least one R 11 , C 6 -C 10 aryl optionally substituted with at least one R 11 , C 6 -C 10 aralkyl optionally substituted with at least one R 11 , NH 2 , NHR 11 , NR 11 R 11 , or SO 2 R 11 , wherein R 11 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 6 -C 10 aryl, C 3 -C 8 aralkyl, C 3 -C 8 heterocyclyl, or NH 2 .
13 . The compound according to claim 8 , wherein R 4 is substituted with R 12 wherein R 12 is independently halo, cyano, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 13 , C 1 -C 4 alkoxy optionally substituted with at least one R 13 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 13 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 13 , C 3 -C 10 aryl optionally substituted with at least one R 13 , NH 2 , NHR 13 , NR 13 R 13 , or SO 2 R 13 , wherein R 13 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 9 aryl, C 3 -C 8 heterocyclylalkyl, or NH 2 .
14 . The compound according to claim 8 , wherein R 6 is substituted with R 9 wherein R 9 is independently hydroxyl, halo, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 14 , C 2 -C 6 alkynyl optionally substituted with at least one R 14 , C 1 -C 6 alkoxy optionally substituted with at least one R 14 , C 3 -C 10 cycloalkyl optionally substituted with at least one R 14 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 14 , C 4 -C 8 cycloalkylalkyl optionally substituted with R 14 , heterocyclylalkyl optionally substituted with R 14 , C 4 -C 10 aryl optionally substituted with at least one R 14 , C 5 -C 10 aralkyl optionally substituted with at least one R 14 , —NH 2 , —NHR 14 , —NR 14 R 14 , or —SO 2 —R 14 , wherein R 14 is independently halo, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 4 -C 9 cycloalkyl, C 4 -C 9 heterocycloalkyl, C 4 -C 10 aryl, —SO 2 (C 6 -C 10 aryl), —NH 2 , —NH[(C 1 -C 4 ) alkyl], —N[(C 1 -C 4 ) alkyl] 2 , —NH(C 5 -C 8 heterocyclylalkyl), —NH(C 6 -C 8 aryl), or —NH(C 6 -C 8 heterocyclyl).
15 . A method for treating cancer comprising administering a therapeutically effective amount of a compound of Formula II to a subject in need of such treatment, wherein the compound of Formula II has the formula:
or pharmaceutically acceptable salts, stereoisomers, hydrates or pro-drugs thereof, wherein,
the ring formed by T, U, V is
Z is O, S, nitro, or NR 4 ;
R 1 , R 2 , or R 5 each independently is:
1) hydrogen, hydroxyl, halo, nitro, or cyano;
2) C 1 -C 6 alkyl;
3) C 2 -C 6 alkenyl;
4) C 2 -C 6 alkynyl;
5) C 1 -C 6 alkoxy;
6) C 3 -C 8 cycloalkyl or heterocyclyl;
7) C 4 -C 8 cycloalkylalkyl or heterocyclylalkyl;
8) C 4 -C 10 aryl;
9) C 5 -C 10 aralkyl;
10) C 6 -C 10 aryloxy;
11) NH 2 , NHR 7 , or NR 7 R 7 ; or
12) —SO 2 R 7 ,
wherein R 7 is independently H, hydroxyl, halo, C 1 -C 4 alkyl optionally substituted with at least one R 10 , C 1 -C 4 alkoxy optionally substituted with at least one R 10 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 10 , C 4 -C 8 heterocycloalkyl optionally substituted with at least one R 10 , C 6 -C 10 aryl optionally substituted with at least one R 10 , NH 2 , NHR 10 , NR 10 R 10 , or SO 2 R 10 , wherein R 10 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or NH 2 , wherein when taken together R 1 and R 2 form a ring structure including heterocyclyl or aryl rings;
R 3 is:
1) hydrogen;
2) C 1 -C 6 alkyl;
3) C 2 -C 6 alkenyl;
4) C 2 -C 6 alkynyl;
5) C 1 -C 6 alkoxy;
6) C 3 -C 10 cycloalkyl or heterocyclyl;
7) C 4 -C 10 cycloalkylalkyl or heterocyclylalkyl;
8) C 4 -C 10 aryl;
9) C 4 -C 10 aralkyl;
10) carbonyl; or
11) —SO 2 R 8 , —CO 2 R 8 , —SR 8 , or —SOR 8 ;
wherein R 8 is independently H, halo, cyano, nitro, C 1 -C 4 alkyl optionally substituted with at least one R 11 , C 1 -C 4 alkoxy optionally substituted with at least one R 11 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 11 , C 3 -C 8 heterocyclyl optionally substituted with at least one R 11 , C 6 -C 10 aryl optionally substituted with at least one R 11 , C 6 -C 10 aralkyl optionally substituted with at least one R 11 , NH 2 , NHR 11 , NR 11 R 11 , or SO 2 R 11 , wherein R 11 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 6 -C 10 aryl, C 3 -C 8 aralkyl, C 3 -C 8 heterocyclyl, or NH 2 ,
R 4 is:
1) hydrogen;
2) C 1 -C 6 alkyl;
3) C 2 -C 6 alkenyl;
4) C 2 -C 6 alkynyl;
5) C 3 -C 8 cycloalkyl or heterocyclyl;
6) C 4 -C 8 cycloalkylalkyl or heterocyclylalkyl;
7) C 4 -C 10 aryl;
8) C 5 -C 10 aralkyl;
9) carbonyl; or
10) —SO 2 R 12 , or —SOR 12 ;
wherein R 12 is independently H, halo, cyano, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 13 , C 1 -C 4 alkoxy optionally substituted with at least one R 13 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 3 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 13 , C 6 -C 10 aryl optionally substituted with at least one R 13 , NH 2 , NHR 13 , NR 13 R 13 , or SO 2 R 13 , wherein R 13 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 9 aryl, C 3 -C 8 heterocyclylalkyl, or NH 2 ; and
R 6 is:
1) C 1 -C 6 alkyl;
2) C 2 -C 6 alkenyl;
3) C 2 -C 6 alkynyl;
4) C 1 -C 6 alkoxy;
5) C 3 -C 8 cycloalkyl or heterocyclyl;
6) C 4 -C 8 cycloalkylalkyl or heterocyclylalkyl;
7) C 4 -C 10 aryl;
8) C 5 -C 10 aralkyl; or
9) —NH 2 , —NHR 9 , or —NR 9 R 9 ,
wherein R 9 is independently hydroxyl, halo, nitro, C 1 -C 4 alkyl optionally substituted with at least one R 14 , C 2 -C 4 alkynyl optionally substituted with at least one R 14 , C 1 -C 4 alkoxy optionally substituted with at least one R 14 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 14 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 14 , C 6 -C 10 aryl optionally substituted with at least one R 14 , C 5 -C 10 aralkyl optionally substituted with at least one R 14 , —NH 2 , —NHR 14 , —NR 14 R 14 , or —SO 2 —R 14 , wherein R 14 is independently halo, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 4 -C 9 cycloalkyl, C 6 -C 10 aryl, C 4 -C 9 heterocycloalkyl, —SO 2 (C 6 -C 10 aryl), NH 2 , —NH[(C 1 -C 4 ) alkyl], —N[(C 1 -C 4 ) alkyl] 2 , —NH(C 5 -C 9 heterocyclylalkyl), —NH(C6-C 8 aryl), or —NH(C 6 -C 8 heterocyclyl) or a pharmaceutically acceptable salt, hydrate or pro-drug thereof, in combination with a pharmaceutically acceptable carrier.
16 . The method according to claim 15 , wherein Z is O or NH.
17 . The method according to claim 15 , wherein R 1 , R 2 , or R 5 is substituted with R 7 wherein R 7 is independently hydroxyl, halo, C 1 -C 6 alkyl optionally substituted with at least one R 10 , C 1 -C 6 alkoxy optionally substituted with at least one R 10 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 10 , C 4 -C 8 heterocycloalkyl optionally substituted with at least one R 10 , C 3 -C 10 aryl optionally substituted with at least one R 10 , NH 2 , NHR 10 , NR 10 R 10 , or SO 2 R 10 , wherein R 10 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, or NH 2 .
18 . The method according to claim 15 , wherein R 1 and R 2 taken together form a ring structure including cycloalkyl, heterocyclyl, or aryl.
19 . The method according to claim 15 , wherein R 3 is substituted with R 8 wherein R 8 is independently halo, cyano, nitro, C 1 -C 4 alkyl optionally substituted with at least one R 11 , C 1 -C 4 alkoxy optionally substituted with at least one R 11 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 11 , C 3 -C 8 heterocyclyl optionally substituted with at least one R 11 , C 6 -C 10 aryl optionally substituted with at least one R 11 , C 6 -C 10 aralkyl optionally substituted with at least one R 11 , NH 2 , NHR 11 , NR 11 R 11 , or SO 2 R 11 , wherein R 11 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 6 -C 10 aryl, C 3 -C 8 aralkyl, C 3 -C 8 heterocyclyl, or NH 2 .
20 . The method according to claim 15 , wherein R 4 is substituted with R 12 wherein R 12 is independently halo, cyano, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 13 , C 1 -C 4 alkoxy optionally substituted with at least one R 13 , C 3 -C 8 cycloalkyl optionally substituted with at least one R 13 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 13 , C 3 -C 10 aryl optionally substituted with at least one R 13 , NH 2 , NHR 13 , NR 13 R 13 , or SO 2 R 13 , wherein R 13 is independently halo, cyano, nitro, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, C 3 -C 9 aryl, C 3 -C 8 heterocyclylalkyl, or NH 2 .
21 . The method according to claim 15 , wherein R 6 is substituted with R 9 wherein R 9 is independently hydroxyl, halo, nitro, C 1 -C 6 alkyl optionally substituted with at least one R 14 , C 2 -C 6 alkynyl optionally substituted with at least one R 14 , C 1 -C 6 alkoxy optionally substituted with at least one R 14 , C 3 -C 10 cycloalkyl optionally substituted with at least one R 14 , C 2 -C 8 heterocyclyl optionally substituted with at least one R 14 , C 4 -C 9 cycloalkylalkyl optionally substituted with R 14 , heterocyclylalkyl optionally substituted with R 14 , C 4 -C 10 aryl optionally substituted with at least one R 14 , C 5 -C 10 aralkyl optionally substituted with at least one R 14 , —NH 2 , —NHR 14 , —NR 14 R 14 , or —SO 2 —R 14 , wherein R 14 is independently halo, cyano, nitro, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, C 4 -C 9 cycloalkyl, C 4 -C 9 heterocycloalkyl, C 4 -C 10 aryl, —SO 2 (C 6 -C 10 aryl), —NH 2 , —NH[(C 1 -C 4 ) alkyl], —N[(C 1 -C 4 ) alkyl] 2 , —NH(C 5 -C 8 heterocyclylalkyl), —NH(C 6 -C 8 aryl), or —NH(C 6 -C 8 heterocyclyl).
22 . The method according to claim 15 , wherein the dosage form is a tablet, caplet, troche, lozenge, dispersion, suspension, suppository, solution, capsule, or patch.
23 . The method according to claim 15 , wherein the compound is administered in about 0.001 mg/kg to about 100 mg/kg.
24 . The method according to claim 15 , wherein the compound is administered by oral administration.Join the waitlist — get patent alerts
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